This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our overall research effort has five components: membrane receptors and cellular signaling, viral proteins and HIV infection, molecular chaperones and protein folding, structural genomics of membrane proteins, and crystallographic methodology. Each of these projects requires synchrotron radiation;while many of the projects can make effective use of the X4 beamlines that we operate at NSLS, others require the brightness of NE-CAT beamlines at APS. Our efforts on membrane receptors currently focus on G-protein coupled receptors, notably serotonin receptors and glycoprotein hormone receptors;on Cys-loop receptors, including acetylcholine and serotonin receptors;on histidine kinase sensors;and on ryanodine receptors. Our efforts on viral proteins currently focus on the HIV envelope protein gp120 and on viral capsid proteins. Our efforts on molecular chaperones include work on the bacterial chaperone trigger factor and on the ubiquitous Hsp70 chaperones. Our efforts in structural genomics of membrane proteins are as part of a consortium of the Protein Structure Initiative that is just now beginning to produce substantial numbers of crystals. Our work on crystallographic methodology currently focuses on the optimization of MAD and SAD phasing methods for challenging problems.